Low miR-223 links to major adverse cardiovascular and cerebrovascular events in end-stage renal disease through endothelial damage

BACKGROUND: End-stage renal disease (ESRD) is frequently accompanied by major adverse cardiac and cerebrovascular events (MACCE) in affected patients. Therefore, there is an urgent need to develop effective biomarkers. METHODS: This prospective study included 112 ESRD patients (62 with MACCE, 50 Non-MACCE), with baseline clinical data and blood samples collected for all subjects. We quantified miR-223 expression through RT-qPCR. To clarify the independent predictive value of miR-223, we conducted multivariate logistic analysis to verify its independent association with the occurrence of MACCE, and drew ROC curves to evaluate its ability to distinguish the occurrence or non-MACCE. Then, we induced inflammation in HUVECs with TNF-α, transfected miR-223 overexpression vectors into these cells, and observed corresponding changes in inflammatory cytokines, adhesion molecules, endothelial markers, nitric oxide metabolites, and cell proliferation. RESULTS: Clinical analysis of ESRD patients revealed that the development of MACCE was associated with significantly lower baseline expression of miR-223 compared to the non-MACCE group. Multivariate analysis confirmed low levels of miR-223 as an independent predictor of MACCE with robust discriminatory ability (AUC = 0.896). In addition, miR-223 levels were inversely related to inflammatory markers (hs-CRP) and serum phosphorus and iPTH. In vitro, miR-223 overexpression suppressed inflammation, the expression of adhesion molecules, ET-1 secretion, normalized nitrite levels, and inhibited aberrant endothelial proliferation. CONCLUSION: This study confirms that reduced miR-223 is an independent predictor of MACCE risk in ESRD patients, with confirmed multifaceted endothelial protective effects in vitro. miR-223 could be a new biomarker integrating multiple risk pathways for cardiovascular risk assessment.